RMSD graph of protein_ligand complex

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1

GROMACS version: 2023.3
GROMACS modification: Yes/No
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Hi all,

I perform MD simulation for protein alone and analyze RMSD. After performing MD simulations for three protein_ligand complexes. Analyze RMSD for 3 pro_lig complexes. Then am compared with protein RMSD and three complexes RMSD. Now

  1. My question is whether protein is stable or not ?
  2. The graph in which complex is stable Pon, RAF and Lor?

image (1)
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2

RMSD is considered as a common metric for comparing two structures. This metric quantifies the average deviation between corresponding atoms, such as C-alphas, in two sets of coordinates (reference and target). Essentially, a smaller RMSD value indicates a higher similarity between the two structures.

The choice of reference is crucial, typically being the protein C-alphas coordinates in the first frame of the trajectory, then the pre-preparation of the trajectory should be taken into account. The alignment process mitigates the impact of molecule rotation and translation in RMSD analysis. Careful consideration of the molecule selected for alignment is essential.

I presume that the x-axis represents time in nanoseconds (ns), while the y-axis represents distance in nanometers (nm) in your plot. I recommend extending your simulations further, perhaps to 200 ns, to achieve convergence (reaching a plateau), as fluctuations are still present. Could you clarify the reference structure? Is it solely the protein in all cases, or do the others represent the root mean square deviation (RMSD) of the protein and bound ligand? Did you align them?

Then, apart from visually examining, I suggest to calculate other metrics e.g. radius of gyration or explore the interaction fingerprints and calculate distance between key residues in the binding site that may represent the binding/unbinding.

For additional details, refer to:
https://manual.gromacs.org/current/onlinehelp/gmx-rms.html
https://manual.gromacs.org/current/onlinehelp/gmx-gyrate.html

3

Thank you for your response FarzaneJP

In the graph blue color is my protein without ligand and My first simulation is run MD Simulation alone for protein. My second simulation is a selected three drugs are RAF, Pon and Lor for MD Simulations with protein (protein is same in alone MD simulation and complexes simulations). After am completed two simulations after Am took the protein (reference) RMSD from alone protein simulation (first simulation) and again took RMSD from three complexes (Protein_lig after lsq fit to Protein_lig) of second simulation. Am running MD Simulations for 100ns. Now I am comparing protein RMSD (reference structure) with three complexes (protein + RAF, protein +Pon and Protein + Lor) RMSD structures.
My questions are

  1. Are the protein and complexes stable or not? And if protein is stable then which complex is good compared to other complex structures?

Based on your suggestion am performing Radius of gyration for a lone protein (reference structure) and three complexes (protein is same in all complexes) after am compared these structures. The image is below attached. Based on my results please give me suggestions and clarify and if I need to perform 200ns simulation for three complexes and alone protein or either these results are sufficient to say my RMSD graph in protein and complexes are stable.

Again thankyou for your patience and response.

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